Early-phase Study of ART002g1 Injection in HeFH: Safety, Tolerability and Preliminary Efficacy

Early Phase 1Not Yet RecruitingNCT07353398

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine24 enrolled

Overview

This study is an open-label, single ascending dose (SAD) study designed to evaluate the safety and tolerability of ART002g1 in patients with heterozygous familial hypercholesterolemia (HeFH) who require further reduction in low-density lipoprotein cholesterol (LDL-C). ART002g1 uses base editing technology, which is designed to interfere with the expression of the PCSK9 gene in the liver, thereby reducing the circulating levels of PCSK9 and LDL-C. The primary objectives of this study are to determine the safety and pharmacodynamic (PD) profiles of ART002g1 in this patient population.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Heterozygous Familial Hypercholesterolemia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Subjects must meet all the following criteria to be eligible for enrollment: 1. Male or female, aged 18 to 70 years (inclusive) at the time of signing the Informed Consent Form (ICF); 2. Body weight between 45 and 90 kg (inclusive) at screening; 3. Definite diagnosis of heterozygous familial hypercholesterolemia (HeFH), meeting either of the following two criteria (1) or (2): （1) HeFH diagnosed to be caused by mutations in the LDLR, APOB, or PCSK9 gene; (2) Meeting 2 out of the 3 following criteria for adults per the Dutch Lipid Clinical Network (DLCN) criteria: 1. Serum LDL-C ≥ 4.7 mmol/L without prior lipid-lowering treatment; 2. Cutaneous or tendinous xanthomas, or arcus cornealis (in subjects \< 45 years old); 3. Presence of FH or early-onset atherosclerotic cardiovascular disease (ASCVD) in first-degree relatives. Subjects must not be enrolled if they meet any one or more of the following exclusion criteria: 1. Diagnosis of compound heterozygous FH, double heterozygous FH, or homozygous FH (HoFH); 2. Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer ≥ 1 × 10² copies/L; positive for hepatitis C virus (HCV) antibody with positive peripheral blood HCV RNA; positive for human immunodeficiency virus (HIV) antibody; 3. Any unstable systemic disease, including but not limited to: unstable angina; cerebrovascular accident or transient ischemic attack (within 6 months prior to screening); myocardial infarction (within 6 months prior to screening); history of heart failure (NYHA Class II-IV); severe arrhythmia requiring pharmacotherapy; liver, kidney, or metabolic diseases; or other unstable systemic diseases as determined by the investigator; 4. History of percutaneous transluminal coronary angioplasty (PTCA), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) within 6 months prior to the first dose; or documented severe coronary artery stenosis as confirmed by coronary CT or coronary angiography within 90 days prior to randomization.

Outcomes

Primary Outcomes

Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Time frame: As of Week 48 (W48) post-administration of ART002g1 for Injection